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Biomedical subjects

M C Evans

Publications and source records attributed to M C Evans.

At least 19 recordsLinked to original sources
PubMed1996

Effect of hormone replacement therapy on bone mineral density in postmenopausal women with mild primary hyperparathyroidism. A randomized, controlled trial.

BACKGROUND: Most patients with primary hyperparathyroidism are postmenopausal women. The presence of osteopenia in persons with mild primary hyperparathyroidism is considered an indication for parathyroidectomy. No prospective, controlled trials have assessed medical therapies for osteopenia in primary hyperparathyroidism. OBJECTIVE: To examine the effects of estrogen-progestin therapy (hormone replacement therapy) on bone mineral density and biochemical indices in postmenopausal women with mild primary hyperparathyroidism. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: University teaching hospital. PATIENTS: 42 postmenopausal women with mild primary hyperparathyroidism. INTERVENTION: Patients were randomly assigned to receive either conjugated estrogens, 0.625 mg/d, and medroxyprogesterone, 5 mg/d, or placebo. MEASUREMENTS: Bone mineral densities of the total body, lumbar spine, proximal femur (femoral neck, Ward triangle, trochanter), and proximal forearm were measured every 6 months using dual-energy x-ray absorptiometry. Biochemical indices of bone turnover and calcium metabolism were measured at baseline, 6 months, and 2 years. RESULTS: In the placebo group, bone mineral densities of the total body and the proximal forearm decreased significantly from baseline (mean +/- SE, -2.3% +/- 0.7% [p = 0.005] and -3.5% +/- 1.2% [p = 0.01], respectively). At the other sites, bone mineral density also tended to decline. In the hormone replacement therapy group, bone mineral density increased from baseline in the total body (1.3% +/- 0.4%; P = 0.004), lumbar spine (5.2% +/- 1.4%; p = 0.002), and femoral neck (3.4% +/- 1.5%; p = 0.05). The between-group differences in bone mineral density at the end of the study ranged from 3.6% to 6.6% and were significant at all sites (P > 0.001 and P < 0.05) except for the Ward triangle (p = 0.06). In the hormone replacement therapy group, serum alkaline phosphatase levels decreased by 22% (p = 0.0004 compared with baseline), urinary hydroxyproline excretion decreased by 42% (p = 0.0004), urinary N-telopeptide excretion decreased by 54% (p = 0.001), and urinary calcium excretion decreased by 45% (p = 0.007). Hormone replacement therapy did not change levels of serum ionized calcium or intact parathyroid hormone. CONCLUSIONS: Although hormone replacement therapy has little effect on serum calcium levels, it suppresses bone turnover, reduces urinary calcium excretion, and increase bone mineral density throughout the skeleton in postmenopausal women with mild primary hyperparathyroidism. This therapy is thus an important management option for these patients.

Aged↗
PubMed1996

Testosterone therapy in glucocorticoid-treated men.

BACKGROUND: Treatment with glucocorticoid drugs is a valuable therapy, but the use of these drugs is associated with major side effects, including osteoporosis, muscle wasting, and obesity. In men who take glucocorticoids, circulating testosterone concentrations are reduced, and this might contribute to the changes in bone and soft-tissue mass. OBJECTIVE: To asses the effect of testosterone replacement on these above-mentioned parameters in glucocorticoid-treated men. METHODS: Fifteen asthmatic men who were receiving long-term glucocorticoid treatment were randomly allocated to receive therapy with testosterone esters (30 mg of proprionate, 60 mg of phenylprionate, 60 mg of isocaproate, and 100 mg of decanoate [Sustanon]) (250-mg/mo intramuscular depot injection) or to act as control subjects during 12 months. After a washout period for those men who were receiving testosterone, the groups were then crossed over and studied for a further 12 months. Bone density and body composition were assessed by dual-energy, x-ray absorptiometry. Paired or unpaired 2-tailed t tested were calculated. Unless otherwise stated, all values are given as mean +/- SEM. RESULTS: Bone density in the lumbar spine increased 5.0% +/- 1.4% (mean +/- SEM) (P = .005) during testosterone supplementation, but it did not change during the control period (between-groups difference, P = .05). These changes were accompanied by a decrease in the indexes of bone turnover. There was a gain in body fat mass (2.1 +/- 0.06 kg, P = .01) and a loss of lean body mass (1.4 +/- 0.5 kg, P = .02) during the control period, with both changes being reversed by testosterone treatment (P < .03). CONCLUSION: Testosterone treatment reverses the deleterious effects glucocorticoid drugs on skeletal and soft tissues in men.

Aged↗
PubMed1996

Photoaccumulation in photosystem I does produce a phylloquinone (A1.-) radical.

Previous work has challenged the assignment of a photoaccumulated EPR signal to the phylloquinone electron acceptor in photosystem I, A1.-. Biosynthetic deuteration of the phylloquinone in the cyanobacterium Anabaena variabilis has been shown to narrow this photoaccumulated signal, demonstrating that the signal arises from A1.-. The ESP signal attributed to P700.+A1.- is also narrowed by this deuteration, showing that the photoaccumulated EPR signal and the ESP signal are monitoring the same redox component. Confirmation that the photoaccumulated EPR signal comes from deuterated phylloquinone was obtained by exchanging the deuterated for protonated phylloquinone, which broadened the photoaccumulated EPR signal.

Anabaena↗
PubMed1996

ENDOR and special triple resonance spectroscopy of A1.- of photosystem 1.

The photoaccumulated radical state of the photosystem 1 secondary electron acceptor A1, A1.-, has been studied in spinach and the cyanobacterium Anabaena variabilis strain Met27 using electron nuclear double resonance (ENDOR) and electron--nuclear--nuclear special triple (ST) resonance spectroscopies. Spectra of A1.- in both these species are very similar. ENDOR spectra of the phylloquinone anion radical in solvent glass were also obtained. Comparison of the spectra of the in vivo and in vitro radicals shows that A1.- is a phylloquinone anion radical with a distorted electron spin density distribution. Hyperfine couplings to the A1.- methyl group and to two protons hydrogen bonded to the quinone oxygens have been identified using biosynthetic deuteration in A. variabilis. Possible hyperfine coupling to a methylene proton of the phytyl side chain of the quinone has also been identified. These results are compared with those from previous studies of protein-bound semiquinones in the light of the unusual redox potential of A1.

Anabaena↗
PubMed1995

ENDOR and special TRIPLE resonance spectroscopy of QA.- of photosystem 2.

ENDOR and special TRIPLE spectroscopies have been used to study the electron spin density distribution and hydrogen bonding of the plastosemiquinone anion radical, QA.-, of photosystem 2. The semiquinone radical was made accessible to ENDOR through the use of exogenous cyanide, which decouples the radical from the ferrous iron of the photosystem 2 ferroquinone acceptor complex [Sanakis, Y., et al. (1994) Biochemistry 33, 9922]. H2O/D2O exchange was used to assign hyperfine couplings to hydrogen-bonded protons, and orientation-selected special TRIPLE spectroscopy has revealed the orientation of hydrogen bonds relative to the quinone ring. Methyl group resonances have also been assigned. ENDOR spectra of the decylplastosemiquinone anion radical in vitro are presented for comparison. This shows that interaction with the protein leads to changes in the electron spin density distribution and the hydrogen bond orientation; both hydrogen bonds are parallel to the quinone ring plane in vitro, whereas QA.- has one parallel and one perpendicular to the plane. These results are discussed in the light of previous ENDOR studies of the ubiquinone radical QA.- of Rhodobacter sphaeroides and the predicted structure of the QA-binding region of photosystem 2.

Benzoquinones↗
PubMed1995

Sources of interracial variation in bone mineral density.

Many studies have demonstrated significant differences in bone mineral density between various racial groups. Although it has been suggested that differences in body weight contribute to such interracial variation, the artifactual effect of the skeletal size inherent in projectional absorptiometry methods has been largely ignored. We have measured bone mineral density by dual-energy X-ray absorptiometry in the lumbar spine and at three femoral sites in 200 premenopausal women of Chinese, Indian, European, or Polynesian origin (50 of similar mean age in each group). In the Chinese and Indian women the measured bone mineral density measurements (g/cm2) were similar, but significantly less, at all sites, than those of European women (p < or = 0.005). The European women were, however, significantly taller than both the Chinese and Indian women (p < 0.0001), and when the scale artifact of absorptiometry was removed by dividing the measured bone mineral density either by the height of the subject, or by the square root of the area over which the X-ray beam was projected, then the differences in mean bone mineral density between the Chinese, Indian, and European women were almost completely eliminated. The Polynesian women were significantly more obese (as judged from mean body mass index) than all the other groups (p < 0.0001) and had significantly greater bone mineral density at all sites than all the other groups both before (p < 0.0001) and after (p < 0.0001) correcting for the scale artifact.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1995

The effect of the antiestrogen tamoxifen on bone mineral density in normal late postmenopausal women.

PURPOSE: To assess the effect of the antiestrogenic agent tamoxifen on bone mineral density in normal late postmenopausal women. METHODS: A randomized, double-blind, placebo-controlled trial was performed with 57 healthy, late postmenopausal women (mean 11 +/- 7 years since menopause). Subjects were assigned to take either tamoxifen 20 mg/d or placebo for 2 years. Total body, lumbar spine, and proximal femoral (femoral neck, Ward's triangle, trochanter) bone mineral densities were measured every 6 months using dual-energy x-ray absorptiometry. Serum and urine indices of bone turnover were measured at baseline, 6 months, and 2 years. RESULTS: In the women given tamoxifen, the mean bone mineral density of the lumbar spine increased by 1.4%, while that in the women given placebo declined by 0.7% (P < 0.01 for difference between groups). Total body bone mineral density declined in both groups, but less so in the tamoxifen-treated women (P < 0.05). At both sites, the effect of tamoxifen was maximal after 1 year, with no further separation of the groups thereafter. There was no significant effect of tamoxifen on bone mineral density in the proximal femur. Tamoxifen produced significant falls in serum alkaline phosphatase (P < 0.0001), ionized calcium (P < 0.0001), and phosphate (P < 0.01), and in urinary excretion of hydroxyproline, n-telopeptides, and calcium (P < 0.05 for each). CONCLUSIONS: In normal late postmenopausal women, tamoxifen at a dose of 20 mg/d exerts a small protective effect on bone mineral density, comparable in magnitude to that of calcium supplementation and less than that of either estrogen or the bisphosphonates. Tamoxifen is unlikely to supersede any of these therapies in the management of postmenopausal osteoporosis.

Absorptiometry, Photon↗
PubMed1995

Long-term effects of calcium supplementation on bone loss and fractures in postmenopausal women: a randomized controlled trial.

PURPOSE: To determine the long-term effects of calcium supplements or placebo on bone density in healthy women at least 3 years postmenopause. PATIENTS AND METHODS: Eighty-six women from our previously reported 2-year study agreed to continue on their double-blind treatment allocation (1 g elemental calcium or placebo) for a further 2 years, with 78 women (40 on placebo) reaching the 4-year end point. Median (interquartile range) dietary calcium intakes for the whole group were 700 mg (range 540 to 910) per day at baseline, 670 mg (range 480 to 890) per day at 2 years, and 640 mg (range 460 to 880) per day at 4 years. The bone mineral density (BMD) of the total body, lumbar spine, and proximal femur was measured every 6 months by dual-energy, x-ray absorptiometry. RESULTS: There was a sustained reduction in the rate of loss of total body BMD in the calcium group throughout the 4-year study period (P = 0.002), and bone loss was significantly less in the calcium-treated subjects in years 2 through 4 also (difference between groups 0.25% +/- 0.11% per year, P = 0.02). In the lumbar spine, bone loss was reduced in the calcium group in year 1 (P = 0.004), but not subsequently. There was, however, a significant treatment effect at this site over the whole 4-year period (P = 0.03). In the proximal femur, the benefit from calcium treatment also tended to be greater in the first year and was significant over the 4-year study period in the femoral neck (P = 0.03) and the trochanter (P = 0.01). Nine symptomatic fractures occurred in 7 subjects in the placebo group and 2 fractures in 2 subjects receiving calcium (P = 0.037). CONCLUSIONS: Calcium supplementation produces a sustained reduction in the rate of loss of total body BMD in healthy postmenopausal women.

Absorptiometry, Photon↗
PubMed1995

The effect of the anti-estrogen tamoxifen on cardiovascular risk factors in normal postmenopausal women.

There is growing interest in the use of anti-estrogens as agents of disease prevention. Studies of women with breast cancer suggest that the synthetic anti-estrogen tamoxifen may reduce the incidence of cardiovascular disease, but the effects of this agent on cardiovascular risk factors in healthy women have not been studied. We have performed a two-year, randomized, placebo-controlled trial to assess the effects of tamoxifen 20 mg/day on serum lipids, fibrinogen, and body composition in 57 normal postmenopausal women. Tamoxifen treatment lowered levels of serum cholesterol by (mean +/- SE) 12 +/- 2%, low density lipoprotein cholesterol by 19 +/- 3%, and fibrinogen by 18 +/- 4% (P < 0.0001 vs. placebo for each). Levels of high density lipoprotein cholesterol were not altered by tamoxifen, but the ratio of total cholesterol to HDL-cholesterol decreased by 11 +/- 4% (P < 0.001 vs. placebo). Tamoxifen did not affect levels of triglycerides, high density lipoprotein cholesterol subfractions, apolipoprotein A1, or glucose, and did not change body weight, body mass index, or body fat distribution. We conclude that tamoxifen significantly reduces the levels of atherogenic lipids and fibrinogen in normal postmenopausal women. The results suggest that the anti-estrogens may substantially reduce the risk of cardiovascular disease, which remains the most common cause of death among postmenopausal women.

Adipose Tissue↗
PubMed1995

Regular exercise dissociates fat mass and bone density in premenopausal women.

Body weight is one of the principal determinants of bone density and fracture frequency, but there is significant disagreement in the literature regarding the relative contributions of the lean and fat components of body weight to this relationship. As previous studies have not considered the possible role of exercise in soft tissue-bone density interrelationships, we measured areal bone mineral density (BMD), fat mass, and lean mass in eumenorrheic premenopausal women and determined whether the interrelationships of these variables are influenced by the subject's exercise status. Subjects with mean activity levels of more than 140 kilojoules/kg.day (equivalent to undertaking vigorous physical activity for > 1.5 h/week) were classified as exercisers. In the nonexercising subjects (n = 36; age, 36 +/- 8 yr), BMD was markedly weight dependent (0.45 < r < 0.62), and this was contributed to by both fat and lean tissue. Because this finding may have arisen from the mutual dependence of soft tissue mass and areal BMD on body size, fat and lean masses were reexpressed as a percentage of body weight. The percent fat tended to be positively related to areal BMD (0.23 < r < 0.35), whereas the percent lean was inversely related to this index. A second way of obviating the mutual dependence of soft tissue mass and areal BMD on body size is to derive BMD/height as an index of volumetric bone density. This parameter was only related to lean mass in the femur, whereas the correlations with fat mass were little changed. The percent fat was positively (0.29 < r < 0.43) and the percent lean was negatively (-0.43 < r < -0.29) related to BMD/height throughout the skeleton, including the femur. In the exercising subjects (n = 63; age, 33 +/- 8 yr), fat mass and lean mass were unrelated to BMD/height (r < 0.23). However, the percent lean was positively correlated with BMD and BMD/height in the femoral neck (r = 0.28 and r = 0.31, respectively). It is concluded that bone density is only associated with fat mass in sedentary women. In exercisers, femoral neck density is related to lean mass, possibly through the effects of weight-bearing exercise on both of these variables.

Adipose Tissue↗
PubMed1994

Investigation of the ammonium chloride and ammonium acetate inhibition of oxygen evolution by Photosystem II.

Using EPR and EXAFS spectroscopies we show that high concentrations of ammonium cations at alkaline pH are required for (1) inhibition of oxygen evolution: (2) an alteration of the EPR properties of the oxygen evolving complex: (3) the ability to detect YZ; and (4) the slow reduction of the Mn complex leading to the appearance of EPR detectable Mn2+. The inhibition of S state cycling, slowing of YZ reduction, appearance of Mn2+ and the yield of a Hpp < 10 mT S3 type EPR signal are decreased by calcium addition. This indicates that these effects were probably associated with calcium depletion arising from the high concentration of ammonium cation. The ammonia-induced changes to the S2 multiline EPR signal are not affected by calcium addition. The appearance of Mn2+ is shown to be reversible on illumination, suggesting that the Mn reduced from the native state is located at or near the native site. Simulations of the interaction which give rise to the S3 EPR signal are also presented and discussed. These indicate that lineshape differences occur through small changes in the exchange component of the interaction between the manganese complex and organic radical, probably through minor structural changes between the variously treated samples.

Acetates↗
PubMed1994

Body weight and bone mineral density in postmenopausal women with primary hyperparathyroidism.

OBJECTIVE: To assess bone mineral density and body composition in postmenopausal women with primary hyperparathyroidism. DESIGN: Cross-sectional study with an age-matched control group. SETTING: University teaching hospital. PATIENTS: 41 postmenopausal women with mild primary hyperparathyroidism and 43 eucalcemic, age-matched controls. MEASUREMENTS: Total body, lumbar spine, and proximal femoral (femoral neck, Ward's triangle, and trochanter) bone mineral density; body composition; and fat distribution were measured using dual-energy x-ray absorptiometry. RESULTS: Women with primary hyperparathyroidism were heavier (75.5 kg compared with 66.3 kg; difference, 9.2 kg [95% CI, 3.7 to 14.7 kg]; P = 0.002), had a higher fat mass (33.3 kg compared with 26.1 kg; difference, 7.2 kg [CI, 3.0 to 11.4 kg]; P = 0.001), and had a more android pattern of fat distribution (android-to-gynoid fat ratio, 1.05 compared with 0.84; difference, 0.21 [CI, 0.1 to 0.32]; P = 0.0004) than the controls. Unadjusted bone mineral density was similar in patients and controls at all sites: total body, 0.990 compared with 1.023 g/cm2 (difference, 0.033; CI, -0.004 to 0.070); posteroanterior lumbar spine, 1.032 compared with 1.018 g/cm2 (difference, 0.014; CI, -0.031 to 0.059); lateral lumbar spine, 0.569 compared with 0.528 g/cm2 (difference, 0.041; CI, -0.022 to 0.104); femoral neck, 0.799 compared with 0.825 g/cm2 (difference, 0.026; CI, -0.072 to 0.124); Ward's triangle, 0.653 compared with 0.677 g/cm2 (difference, 0.024; CI, -0.035 to 0.089); trochanter, 0.734 compared with 0.733 g/cm2 (difference, 0.001; CI, -0.024 to 0.026); and arms, 0.720 compared with 0.739 g/cm2 (difference, 0.019; CI, -0.015 to 0.053). After adjustment for body weight, bone mineral density in women with primary hyperparathyroidism was lower than that in controls for total body (P = 0.0004), femoral neck (P = 0.001), Ward's triangle (P = 0.01), trochanter (P = 0.02), and arms (P = 0.0006). Spinal bone mineral density did not differ between groups. CONCLUSIONS: Body weight, total body fat mass, and proportion of android fat are increased in postmenopausal women with primary hyperparathyroidism; these unexplained factors may be relevant to the increased incidence of cardiovascular disease in this condition. Unadjusted bone mineral density values are similar in patients with primary hyperparathyroidism and in controls, suggesting that this condition is not associated with an increased risk for fracture.

Adipose Tissue↗
PubMed1994

Path of electron transfer in photosystem 1: direct evidence of forward electron transfer from A1 to Fe-Sx.

Pulsed EPR spectroscopy and selective removal of the iron-sulfur centers in photosystem 1 have been used to study forward electron transfer from the secondary electron acceptor A1. At cryogenic temperatures where forward electron transfer is inhibited, we have observed a g = 2.003 electron spin-echo signal presenting a characteristic phase shift. This out-of-phase signal is attributed to the electron spin-polarized pair P700+/A1-, it decays with t1/e = 23 microseconds, reflecting the recombination reaction. At room temperature the out-of-phase signal is also observed, but it decays with t1/c = 200 ns in untreated photosystem 1, due to forward electron transfer from A1- to one of the iron-sulfur centers. This rate is unchanged in Fe-SA/B-depleted PS1 but is lost when the iron-sulfur center Fe-Sx is removed. In the preparations depleted of all iron-sulfur centers the out-of-phase signal decays with t1/c = 1.3 microseconds, reflecting either the back reaction or the decay of polarization. These results demonstrate that the electron transfer pathway in photosystem 1 is P700-->A1-->Fe-SX-->Fe-SA/B.

Chlorophyll↗
PubMed1994

The electronic structure of P840+. The primary donor of the Chlorobium limicola f. sp. thiosulphatophilum photosynthetic reaction centre.

The radical cation P840+. was studied in frozen suspensions of Chlorobium limicola f. sp. thiosulphatophilum membranes using ENDOR and Special TRIPLE spectroscopies. The spectra show that P840+. arises from a bacteriochlorophyll a 'special' pair with a highly symmetrical distribution of electron spin density between the constituent bacteriochlorophylls. Special TRIPLE spectroscopy has resolved the separate contributions of the two halves of the pair and revealed small deviations from a 1:1 electron spin density distribution. Nevertheless P840+. appears to come the closest yet to the symmetrical 'dimer' originally proposed for the structure of the primary donor radical cation (P870+.) in purple non-sulphur photosynthetic bacteria.

Bacteria↗
PubMed1994

Volumetric bone density of the lumbar spine is related to fat mass but not lean mass in normal postmenopausal women.

We have previously found that fat mass but not lean body mass is related to bone mineral density (BMD) in women. In these and most other studies of the dependence of BMD on body composition, areal rather than volumetric bone density was measured. It is possible that the dependence of this variable on body size introduced a scale artifact that contributed to the previous findings. The present study addresses this issue by measuring the volumetric density of the third lumbar vertebra from simultaneous anteroposterior (AP) and lateral scans using dual-energy X-ray absorptiometry in 119 normal postmenopausal women. Whole body fat and lean body mass were also measured using this technique. In the AP projection, BMD was similarly related to body weight and to fat mass (r = 0.44, p < 0.0001 for both) but not to lean body mass (r = 0.17, NS). BMD in the lateral projection was less closely related to body composition than was AP BMD, but the greater impact of fat (r = 0.25, p < 0.01) than lean body mass (r = 0.09, NS) was still evident. When AP or lateral BMDs were divided by height, arm span or the square root of the scan area to produce an index with the dimensions of volumetric density, the dependence of BMD on body weight and fat mass was not affected but the relationship to lean body mass was eliminated (-0.02 < r < 0.09). Similarly, the volumetric density of the third lumbar vertebra was related to fat mass (r = 0.21, p = 0.02) but not to lean body mass (r = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗